1. Genetic contributors to serum uric acid levels in Mexicans and their effect on premature coronary artery disease
- Author
-
Carla Gallo, Paola León-Mimila, Luis Macías-Kauffer, Sofia Moran-Ramos, Andres Ruiz-Linares, Leonor Jacobo-Albavera, Christopher R. Stephens, Victor Acuña-Alonzo, Maria Cátira Bortolini, Francisco J. Flores-Murrieta, Sandra Romero-Hidalgo, Blanca E. Del-Rio-Navarro, Carlos A. Aguilar-Salinas, Teresa Villarreal-Molina, Hugo Villamil-Ramírez, Rolando González-José, Gabriel Bedoya, Carlos Posadas-Romero, Francisco Rothhammer, Rosalinda Posadas-Sánchez, Gilberto Vargas-Alarcón, Cecilia Fernández del Valle-Laisequilla, Samuel Canizales-Quinteros, Blanca E. López-Contreras, Miriam del Carmen Carrasco-Portugal, Rafael Velázquez-Cruz, Lina M. Barranco Garduño, Juan Gerardo Reyes-García, Anthropologie bio-culturelle, Droit, Ethique et Santé (ADES), Aix Marseille Université (AMU)-EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique (CNRS), Dept of Genetics, Evolution and Environment [London] (UCL-GEE), University College of London [London] (UCL), Instituto Nacional de Cardiología, Molecular Genetics Laboratory, Escuela Nacional de Antropologia y Historia, Laboratorio de Genética Molecular, Universidad de Antioquia = University of Antioquia [Medellín, Colombia], Facultad de Medicina & Instituto de Alta Investigacion, Universidad de Tarapaca-Universidade de Chile, Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET), Universidad Nacional Autónoma de México (UNAM), Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán - National Institute of Medical Science and Nutrition Salvador Zubiran [Mexico], and Unit of Molecular Biology and Genomic Medicine
- Subjects
Male ,obesity ,estimated glomerular filtration rate ,ABCG2 gene ,genotype ,[SDV]Life Sciences [q-bio] ,[SHS.ANTHRO-BIO]Humanities and Social Sciences/Biological anthropology ,Genome-wide association study ,Coronary Artery Disease ,030204 cardiovascular system & hematology ,Bioinformatics ,Coronary artery disease ,Genética y Herencia ,0302 clinical medicine ,single nucleotide polymorphism ,genetic variability ,gender ,purl.org/pe-repo/ocde/ford#3.02.04 [https] ,030212 general & internal medicine ,Child ,ComputingMilieux_MISCELLANEOUS ,Aged, 80 and over ,child ,biology ,adult ,Mexican ,Mendelian Randomization Analysis ,Middle Aged ,cohort analysis ,3. Good health ,aged ,female ,priority journal ,breast cancer resistance protein ,Female ,Cardiology and Cardiovascular Medicine ,CIENCIAS NATURALES Y EXACTAS ,uric acid blood level ,Adult ,gene locus ,Adolescent ,GENETICS ,Mendelian randomization analysis ,Single-nucleotide polymorphism ,Polymorphism, Single Nucleotide ,Article ,Ciencias Biológicas ,03 medical and health sciences ,Young Adult ,male ,Mendelian randomization ,medicine ,SNP ,Humans ,controlled study ,human ,gene ,Mexico ,Aged ,genome-wide association study ,business.industry ,medicine.disease ,major clinical study ,Uric Acid ,URIC ACID ,SLC2A9 gene ,biology.protein ,CORONARY ARTERY DISEASE ,metabolic syndrome X ,Metabolic syndrome ,business ,Biomarkers ,SLC2A9 ,Genome-Wide Association Study - Abstract
Background: Serum uric acid (SUA) is a heritable trait associated with cardiovascular risk factors and coronary artery disease (CAD). Genome wide association studies (GWAS) have identified several genes associated with SUA, mainly in European populations. However, to date there are few GWAS in Latino populations, and the role of SUA-associated single nucleotide polymorphisms (SNPs) in cardiovascular disease has not been studied in the Mexican population. Methods: We performed genome-wide SUA association study in 2153 Mexican children and adults, evaluated whether genetic effects were modified by sex and obesity, and used a Mendelian randomization approach in an independent cohort to study the role of SUA modifying genetic variants in premature CAD. Results: Only two loci were associated with SUA levels: SLC2A9 (β = −0.47 mg/dl, P = 1.57 × 10−42 for lead SNP rs7678287) and ABCG2 (β = 0.23 mg/dl, P = 2.42 × 10−10 for lead SNP rs2231142). No significant interaction between SLC2A9 rs7678287 and ABCG2 rs2231142 genotypes and obesity was observed. However, a significant ABCG2 rs2231142 genotype*sex interaction (P = 0.001) was observed in adults but not in children. Although SUA levels were associated with premature CAD, metabolic syndrome and decreased glomerular filtration rate (eGFR), only ABCG2 rs2231142 was associated with decreased eGFR in the premature CAD group. Conclusions: SUA elevation was independently associated with premature CAD, metabolic syndrome and decreased eGFR in the Mexican population. However, a Mendelian randomization approach using the lead SUA-associated SNPs (SLC2A9 and ABCG2) did not support a causal role of elevated SUA levels for premature CAD. Fil: Macias Kauffer, Luis R.. Instituto Nacional de Medicina Genómica Mexico; México. Universidad Nacional Autónoma de México; México Fil: Villamil Ramírez, Hugo. Instituto Nacional de Medicina Genómica Mexico; México Fil: León Mimila, Paola. Instituto Nacional de Medicina Genómica Mexico; México Fil: Jacobo Albavera, Leonor. Inmegen; México Fil: Posadas Romero, Carlos. Instituto Nacional de Cardiologia Ignacio Chavez; México Fil: Posadas Sánchez, Rosalinda. Instituto Nacional de Cardiologia Ignacio Chavez; México Fil: López Contreras, Blanca E.. Instituto Nacional de Medicina Genómica Mexico; México Fil: Morán Ramos, Sofía. Instituto Nacional de Medicina Genómica Mexico; México Fil: Romero Hidalgo, Sandra. Inmegen; México Fil: Acuña Alonzo, Víctor. Colegio Universitario de Londres; Reino Unido Fil: del Río Navarro, Blanca E.. Hospital Infantil de Mexico Federico Gomez; México Fil: Bortolini, Maria Cátira. Universidade Federal do Rio Grande do Sul; Brasil Fil: Gallo, Carla. Universidad Peruana Cayetano Heredia; Perú Fil: Bedoya, Gabriel. Universidad de Antioquia; Colombia Fil: Rothhammer, Francisco. Universidad de Chile; Chile Fil: González José, Rolando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico de Ciencias Sociales y Humanas; Argentina Fil: Ruiz-Linares, Andres. Fudan University; China. Anthropologie Bio-culturelle, Droit, Éthique & Fil: Stephens, Christopher R.. Universidad Nacional Autónoma de México. Instituto de Ciencias Nucleares; México Fil: Velazquez Cruz, Rafael. Instituto Nacional de Medicina Genómica Mexico; México Fil: Fernández del Valle Laisequilla, Cecilia. Productos Medix; México Fil: Reyes-García, Juan G.. INSTITUTO POLITÉCNICO NACIONAL (IPN); Fil: Barranco Garduño, Lina M.. Instituto Nacional de Enfermedades Respiratorias; México Fil: Carrasco-Portugal, Miriam del C.. Instituto Nacional de Enfermedades Respiratorias; México Fil: Flores-Murrieta, Francisco J.. Instituto Nacional de Enfermedades Respiratorias; México. INSTITUTO POLITÉCNICO NACIONAL (IPN); Fil: Vargas Alarcón, Gilberto. Instituto Nacional de Cardiologia Ignacio Chavez; México Fil: Aguilar Salinas, Carlos A.. Escuela de Medicina y Ciencias de la Salud Tecsalud; México. Instituto Nacional de la Nutrición Salvador Zubiran; México Fil: Villarreal Molina, Teresa. Inmegen; México Fil: Canizales Quinteros, Samuel. Instituto Nacional de Medicina Genómica Mexico; México
- Published
- 2019
- Full Text
- View/download PDF